Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction between human immunodeficiency virus type 1 (HIV-1) and RNA silencing pathways is complex and multifaceted. Essential for efficient viral transcription and supporting Tat-mediated transactivation of viral gene expression, the trans-activation responsive (TAR) element is a structured RNA located at the 5' end of all transcripts derived from HIV-1. Here, we report that this element is a source of microRNAs (miRNAs) in cultured HIV-1-infected cell lines and in HIV-1-infected human CD4+ T lymphocytes. Using primer extension and ribonuclease (RNase) protection assays, we delineated both strands of the TAR miRNA duplex deriving from a model HIV-1 transcript, namely miR-TAR-5p and miR-TAR-3p. In vitro RNase assays indicate that the lack of a free 3' extremity at the base of TAR may contribute to its low processing reactivity in vivo. Both miR-TAR-5p and miR-TAR-3p down-regulated TAR miRNA sensor activity in a process that required an integral miRNA-guided RNA silencing machinery. miR-TAR-3p exerted superior gene downregulatory effects, probably due to its preferential release from HIV-1 TAR RNA by the RNase III Dicer. Our study suggests that the TAR element of HIV-1 transcripts releases functionally competent miRNAs upon asymmetrical processing by Dicer, thereby providing novel insights into viral miRNA biogenesis.
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PMID:Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. 1829 84

In this study, we investigated an RNA (R-Psi-sgRNA) that suppresses HIV-1 replication. This RNA is expressed by a plasmid vector (pR-Psi-sgRNA-ter) that was constructed accidentally. To examine if this effect is caused by RNA interference, R-Psi-sgRNA was synthesized in vitro and treated with the Dicer enzyme, an important RNase III enzyme for RNA interference. The RNA was cleaved into fragments of approximately 20 nucleotides. We then performed an HIV-1 p24 assay with the RNA fragments to evaluate their effect on HIV-1 replication. HIV-1 replication was suppressed.
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PMID:Micro RNA like inhibition of HIV-1 replication. 1877 77

The transactivating response (TAR) RNA-binding protein (TRBP) has been identified as a double-stranded RNA (dsRNA)-binding protein, which associates with a stem-loop region known as the TAR element in human immunodeficiency virus-1 (HIV-1). However, TRBP is also known to be an enhancer of RNA silencing, interacting with Dicer, an enzyme that belongs to the RNase III family. Dicer cleaves long dsRNA into small dsRNA fragments called small interfering RNA or microRNA (miRNA) to mediate RNA silencing. During HIV-1 infection, TAR RNA-mediated translation is suppressed by the secondary structure of 5'UTR TAR RNA. However, TRBP binding to TAR RNA relieves its inhibitory action of translation and Dicer processes HIV-1 TAR RNA to generate TAR miRNA. However, whether the interaction between TRBP and Dicer is necessary for TAR RNA translation or TAR miRNA processing remains unclear. In this study, we constructed TRBP mutants that were unable to interact with Dicer by introducing mutations into amino acid residues necessary for the interaction. Furthermore, we established cell lines expressing such TRBP mutants. Then, we revealed that the TRBP-Dicer interaction is essential for both the TAR-containing RNA translation and the TAR miRNA processing in HIV-1.
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PMID:TRBP-Dicer interaction may enhance HIV-1 TAR RNA translation via TAR RNA processing, repressing host-cell apoptosis. 3205 Nov 9


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